Cellular Aging: Basic Phenomena

The steady loss of replicative potential is accompanied by a greater heterogeneity of cell sizes; cells near the end of their proliferative capacity tend to be much larger than those that have doubled a small number of times. A number of subcellular structures also change with age (see Figure 1). An increase in nuclear size, in nucleolar size, and in the number of multinucleated cells parallels the increase in cell size seen in slowly replicating or nonreplicating cells. Prominent Golgi apparati, evacuated endoplasmic reticula, increased numbers of cytoplasmic microfilaments, vacuolated cytoplasm, and large lysosomal bodies have been observed in senescent human fibroblasts.

Cultures near the end of their proliferative potential display a reduced harvest density and a lowered saturation density at the plateau phase of growth; that is, the number of cells per unit area is lower in near-senescent cultures that exhibit inhibition of growth due to contact with neighboring cells. At the end of their life span in vitro, substantial cell death occurs; however, a stable population emerges that can exist in a viable, nonproliferative state for many months. This stable population is capable of maintaining only an extremely low saturation density, equivalent to less than 5 percent of that reached by cultures that have doubled a small number of times. The observed decrease in saturation densities probably reflects an increased sensitivity to intercellular contact, rather than increased numbers of larger cells. Changes at the level of extracellular matrix (ECM; proteins secreted by the cell that remain attached to the cell), specific secretory proteins not connected with the ECM, and membrane-associated molecules occur in cells near the end of their proliferative life, but it is unclear whether they account for alterations in the nature of cell contact among these cells.